Rashna Balsara received B.S. and Ph.D. degrees from the University of Bombay (India). She was a post-doctoral fellow at the University of Notre Dame from 2002-2005 and Walther Cancer Research Center Fellow 2005-2007. She is currently Research Assistant Professor in the Department of Chemistry and Biochemistry in the W. M. Keck Center for Transgene Research at the University of Notre Dame.
Angiogenesis is an important process of forming new vessels that occurs in both physiological and pathophysiological settings. This process is a multistep event involving several proteins that function in a spatially and temporally controlled microenvironment. Components of the fibrinolytic pathway, namely plasminogen (Pg), urokinase plasminogen activator (uPA), its receptor (uPAR), tissue-type plasminogen activator (tPA), and the physiological inhibitor plasminogen activator inhibitor-1 (PAI-1) are some of the key players involved in angiogenic events. The process of angiogenesis is initiated by activation of the normally quiescent endothelial cells, degradation of the extracellular matrix, followed by cellular proliferation, migration, adhesion, and finally formation of capillary sprouts. Discerning the involvement of the individual fibrinolytic proteins in angiogenesis has been facilitated by utilizing primary endothelial cells obtained from various knockout mice (PAI-1-/-, uPA-/-, uPAR-/-, tPA-/-).
The fibrinolytic proteins are also known to transduce cell signaling by activation of tyrosine kinase receptors, such as, VEGR1 and VEGFR-2 to promote cell survival. Our studies have implicated a novel role of PAI-1 in modulating the Akt, and the JAK/STAT pathway thereby affecting endothelial apoptosis and cell cycle progression. Current studies involve elucidating the role of uPAR in endothelial cell adhesion and its ability to affect cell morphology. Organization of F-actin fibers, and cellular localization of phosphorylated Focal Adhesion Kinase (FAK) and vincullin are dramatically different in uPAR-/- endothelial cells compared to the WT cells. Furthermore, the ability of the receptor to modulate changes in cell morphology and adhesion is dependent on uPAR-mediated cell binding to the matrix via regulation of integrin signaling.
Therefore, the primary focus of interest is to study the role of fibrinolytic pathway components in events associated with angiogenesis, as well as to provide mechanisms by evaluating the underlying signal transduction pathways. The angiogenic study involves cell-based assays, molecular biology, and recombinant protein work, as well as utilizing cutting edge technology, such as, confocal microscopy and real-time microscopy.
- Johnson, J.J.; Miller, D.L.; Jiang, R.; Liu, Y.Y.; Shi, Z.G.; Tarwater, L.; Williams, R.; Balsara, R.D.; Sauter, E.R.; Stack, M.S. "Protease-activated Receptor-2 (PAR-2)-mediated Nf-B Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma." J. Biol. Chem. 2016, 291(13), 6936-6945.
- Cheriyan, J.; Balsara, R.D.; Hansen, K.B.; Castellino, F.J. "Pharmacology of triheteromeric N-Methyl-D-Aspartate Receptors." Neurosci. Lett. 2016, 617, 240-246.
- Kunda, S.; Yuan, Y.; Balsara, R.D.; Zajicek, J.; Castellino, F.J. "Hydroxyproline-induced Helical Disruption in Conantokin RI-B Affects Subunit-selective Antagonistic Activities toward Ion Channels of N-Methyl-D-aspartate Receptors." J. Biol. Chem. 2015, 290(29), 18156-18172.
- Balsara, R.D.; Dang, A.; Donahue, D.L.; Snow, T.; Castellino, F.J. "Conantokin-G Attenuates Detrimental Effects of NMDAR Hyperactivity in an Ischemic Rat Model of Stroke." PLoS One 2015, 10(3), e0122840.
- Cheriyan, J.; Mezes, C.; Zhou, N.; Balsara, R.D.; Castellino, F.J. "Heteromerization of Ligand Binding Domains of N-Methyl-D-Aspartate Receptor Requires Both Coagonists, L-Glutamate and Glycine." Biochemistry 2015, 54(3), 787-794.
- Balsara, R.D.; Chapman, S.E.; Sander, I.M.; Donahue, D.L.; Liepert, L.; Castellino, F.J.; Leevy, W.M. "Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with F-18-FDG." J. Vis. Exp. 2014, 94, e51495.